Hentschel Anouk E, Nieuwenhuijzen Jakko A, Bosschieter Judith, Splunter Annina P van, Lissenberg-Witte Birgit I, Voorn J Patrick van der, Segerink Loes I, Moorselaar R Jeroen A van, Steenbergen Renske D M
Urology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, de Boelelaan 1118, 1182 DB Amsterdam, The Netherlands.
Pathology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, de Boelelaan 1118, 1182 DB Amsterdam, The Netherlands.
Cancers (Basel). 2020 Apr 2;12(4):859. doi: 10.3390/cancers12040859.
DNA methylation analysis of full void urine and urine pellet seems promising for bladder cancer (BC) detection and surveillance. Urinary cell-free DNA from urine supernatant is now gaining interest for other molecular tests in BC. This study aims to evaluate which urine fraction is preferred for BC diagnosis using methylation markers: full void urine, urine pellet or supernatant. Methylation levels of nine markers were determined in the three urine fractions and correlated with their respective tumor tissues in BC patients and compared to controls. For all markers and marker panel , diagnostic performance was determined by calculating the area under the curve (AUC) of the respective receiver operating characteristic curves. For most of the markers, there was a significant correlation between the methylation levels in each of the urine fractions and the matched tumor tissues. Urine pellet was the most representative fraction. Generally, AUCs for BC diagnosis were comparable among the fractions. The highest AUC was obtained for in urine pellet: AUC 0.87 (95% confidence interval: 0.73-1.00), corresponding to a sensitivity of 78.6% and a specificity of 91.7%. Our results demonstrate that cellular and cell-free DNA in urine can be used for BC diagnosis by urinary methylation analysis. Based on our comparative analysis and for practical reasons, we recommend the use of urine pellet.
对全程晨尿和尿沉渣进行DNA甲基化分析在膀胱癌（BC）检测和监测方面似乎很有前景。来自尿液上清液的游离DNA目前在膀胱癌的其他分子检测中受到关注。本研究旨在评估使用甲基化标记物进行BC诊断时，哪种尿液成分更具优势：全程晨尿、尿沉渣还是上清液。测定了三种尿液成分中九种标记物的甲基化水平，并将其与BC患者各自的肿瘤组织进行关联，同时与对照组进行比较。对于所有标记物和标记物组合，通过计算各自的受试者工作特征曲线的曲线下面积（AUC）来确定诊断性能。对于大多数标记物，每种尿液成分中的甲基化水平与匹配的肿瘤组织之间存在显著相关性。尿沉渣是最具代表性的成分。一般来说，各成分在BC诊断中的AUC相当。尿沉渣中获得的最高AUC为：AUC 0.87（95%置信区间：0.73 - 1.00），对应灵敏度为78.6%，特异性为91.7%。我们的结果表明，尿液中的细胞DNA和游离DNA可用于通过尿液甲基化分析进行BC诊断。基于我们的比较分析以及实际原因，我们建议使用尿沉渣。
